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Crystal structure of a protein repair methyltransferase from Pyrococcus furiosus with its L-isoaspartyl peptide substrate.

Griffith SC, Sawaya MR, Boutz DR, Thapar N, Katz JE, Clarke S, Yeates TO
J Mol Biol 313 1103-16 (2001)
Related entries: 1jg1, 1jg3, 1jg4

Cited: 30 times
EuropePMC logo PMID: 11700066

Abstract

Protein L-isoaspartyl (D-aspartyl) methyltransferases (EC 2.1.1.77) are found in almost all organisms. These enzymes catalyze the S-adenosylmethionine (AdoMet)-dependent methylation of isomerized and racemized aspartyl residues in age-damaged proteins as part of an essential protein repair process. Here, we report crystal structures of the repair methyltransferase at resolutions up to 1.2 A from the hyperthermophilic archaeon Pyrococcus furiosus. Refined structures include binary complexes with the active cofactor AdoMet, its reaction product S-adenosylhomocysteine (AdoHcy), and adenosine. The enzyme places the methyl-donating cofactor in a deep, electrostatically negative pocket that is shielded from solvent. Across the multiple crystal structures visualized, the presence or absence of the methyl group on the cofactor correlates with a significant conformational change in the enzyme in a loop bordering the active site, suggesting a role for motion in catalysis or cofactor exchange. We also report the structure of a ternary complex of the enzyme with adenosine and the methyl-accepting polypeptide substrate VYP(L-isoAsp)HA at 2.1 A. The substrate binds in a narrow active site cleft with three of its residues in an extended conformation, suggesting that damaged proteins may be locally denatured during the repair process in cells. Manual and computer-based docking studies on different isomers help explain how the enzyme uses steric effects to make the critical distinction between normal L-aspartyl and age-damaged L-isoaspartyl and D-aspartyl residues.

Reviews - 1jg2 mentioned but not cited (1)

  1. Many paths to methyltransfer: a chronicle of convergence. Schubert HL, Blumenthal RM, Cheng X. Trends Biochem Sci 28 329-335 (2003)

Articles - 1jg2 mentioned but not cited (2)

  1. An Ancient Fingerprint Indicates the Common Ancestry of Rossmann-Fold Enzymes Utilizing Different Ribose-Based Cofactors. Laurino P, Tóth-Petróczy Á, Meana-Pañeda R, Lin W, Truhlar DG, Tawfik DS. PLoS Biol 14 e1002396 (2016)
  2. CASP5 target classification. Kinch LN, Qi Y, Hubbard TJ, Grishin NV. Proteins 53 Suppl 6 340-351 (2003)


Reviews citing this publication (4)

  1. Aging as war between chemical and biochemical processes: protein methylation and the recognition of age-damaged proteins for repair. Clarke S. Ageing Res Rev 2 263-285 (2003)
  2. Protein production in Escherichia coli for structural studies by X-ray crystallography. Goulding CW, Perry LJ. J Struct Biol 142 133-143 (2003)
  3. Structures of SET domain proteins: protein lysine methyltransferases make their mark. Yeates TO. Cell 111 5-7 (2002)
  4. Novel aspects of macromolecular repair and relationship to human disease. Krokan HE, Kavli B, Slupphaug G. J Mol Med (Berl) 82 280-297 (2004)

Articles citing this publication (23)

  1. Structure of the catalytic domain of human DOT1L, a non-SET domain nucleosomal histone methyltransferase. Min J, Feng Q, Li Z, Zhang Y, Xu RM. Cell 112 711-723 (2003)
  2. A novel 3-methylhistidine modification of yeast ribosomal protein Rpl3 is dependent upon the YIL110W methyltransferase. Webb KJ, Zurita-Lopez CI, Al-Hadid Q, Laganowsky A, Young BD, Lipson RS, Souda P, Faull KF, Whitelegge JP, Clarke SG. J Biol Chem 285 37598-37606 (2010)
  3. Discrimination between closely related cellular metabolites by the SAM-I riboswitch. Montange RK, Mondragón E, van Tyne D, Garst AD, Ceres P, Batey RT. J Mol Biol 396 761-772 (2010)
  4. Biological processes and signal transduction pathways regulated by the protein methyltransferase SETD7 and their significance in cancer. Batista IAA, Helguero LA. Signal Transduct Target Ther 3 19 (2018)
  5. An ATP-independent strategy for amide bond formation in antibiotic biosynthesis. Funabashi M, Yang Z, Nonaka K, Hosobuchi M, Fujita Y, Shibata T, Chi X, Van Lanen SG. Nat Chem Biol 6 581-586 (2010)
  6. A post-translational modification of human Norovirus capsid protein attenuates glycan binding. Mallagaray A, Creutznacher R, Dülfer J, Mayer PHO, Grimm LL, Orduña JM, Trabjerg E, Stehle T, Rand KD, Blaum BS, Uetrecht C, Peters T. Nat Commun 10 1320 (2019)
  7. Crystal structure of aclacinomycin-10-hydroxylase, a S-adenosyl-L-methionine-dependent methyltransferase homolog involved in anthracycline biosynthesis in Streptomyces purpurascens. Jansson A, Niemi J, Lindqvist Y, Mäntsälä P, Schneider G. J Mol Biol 334 269-280 (2003)
  8. Differences in α-Crystallin isomerization reveal the activity of protein isoaspartyl methyltransferase (PIMT) in the nucleus and cortex of human lenses. Lyon YA, Sabbah GM, Julian RR. Exp Eye Res 171 131-141 (2018)
  9. Structural and functional insights into O-methyltransferase from Bacillus cereus. Cho JH, Park Y, Ahn JH, Lim Y, Rhee S. J Mol Biol 382 987-997 (2008)
  10. Bioinformatics-Guided Expansion and Discovery of Graspetides. Ramesh S, Guo X, DiCaprio AJ, De Lio AM, Harris LA, Kille BL, Pogorelov TV, Mitchell DA. ACS Chem Biol 16 2787-2797 (2021)
  11. Aspartate Glycosylation Triggers Isomerization to Isoaspartate. Janetzko J, Walker S. J Am Chem Soc 139 3332-3335 (2017)
  12. Thermal-stable proteins of fruit of long-living Sacred Lotus Nelumbo nucifera Gaertn var. China Antique. Shen-Miller J, Lindner P, Xie Y, Villa S, Wooding K, Clarke SG, Loo RR, Loo JA. Trop Plant Biol 6 (2013)
  13. Crystal structure and functional characterization of an isoaspartyl dipeptidase (CpsIadA) from Colwellia psychrerythraea strain 34H. Park SH, Lee CW, Lee SG, Shin SC, Kim HJ, Park H, Lee JH. PLoS One 12 e0181705 (2017)
  14. Crystal structure of pentapeptide-independent chemotaxis receptor methyltransferase (CheR) reveals idiosyncratic structural determinants for receptor recognition. Batra M, Sharma R, Malik A, Dhindwal S, Kumar P, Tomar S. J Struct Biol 196 364-374 (2016)
  15. An Unusually Rapid Protein Backbone Modification Stabilizes the Essential Bacterial Enzyme MurA. Zhang T, Hansen K, Politis A, Müller MM. Biochemistry 59 3683-3695 (2020)
  16. Crystal structure of the protein L-isoaspartyl methyltransferase from Escherichia coli. Fang P, Li X, Wang J, Xing L, Gao Y, Niu L, Teng M. Cell Biochem Biophys 58 163-167 (2010)
  17. Isoaspartylation appears to trigger small cell lung cancer-associated autoimmunity against neuronal protein ELAVL4. Pulido MA, DerHartunian MK, Qin Z, Chung EM, Kang DS, Woodham AW, Tsou JA, Klooster R, Akbari O, Wang L, Kast WM, Liu SV, Verschuuren JJGM, Aswad DW, Laird-Offringa IA. J Neuroimmunol 299 70-78 (2016)
  18. Mechanistic Analysis of the Biosynthesis of the Aspartimidylated Graspetide Amycolimiditide. Choi B, Elashal HE, Cao L, Link AJ. J Am Chem Soc 144 21628-21639 (2022)
  19. The V119I polymorphism in protein L-isoaspartate O-methyltransferase alters the substrate-binding interface. Rutherford K, Daggett V. Protein Eng Des Sel 22 713-721 (2009)
  20. A conformational switch in the active site of BT_2972, a methyltransferase from an antibiotic resistant pathogen B. thetaiotaomicron. Kumar V, Sivaraman J. PLoS One 6 e27543 (2011)
  21. Functional divergence of annotated l-isoaspartate O-methyltransferases in an α-proteobacterium. Yin L, Harwood CS. J Biol Chem 294 2854-2861 (2019)
  22. Human Protein-l-isoaspartate O-Methyltransferase Domain-Containing Protein 1 (PCMTD1) Associates with Cullin-RING Ligase Proteins. Warmack RA, Pang EZ, Peluso E, Lowenson JD, Ong JY, Torres JZ, Clarke SG. Biochemistry 61 879-894 (2022)
  23. Mycobacterial MMAR_2193 catalyzes O-methylation of diverse polyketide cores. Giri GR, Saxena P. PLoS One 17 e0262241 (2022)


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